Synthesis and in silico investigation of Schiff base derivatives of 1H-indole-2,3-diones and their Co(II) and Ni(II) complexes as antimicrobial agents

Abstract

3-[(2-aminophenyl)imino]-1,3-dihydro-2H-indol-2-one, (Lo), 1,3-phenylenediazanylylidene di (1,3-dihydro-2H-indol-2-one), (Lm) and 1,4-phenylenediazanylylidene di(1,3-dihydro-2H-indol-2-one) (Lp) were synthesized by the reaction of 1H-indole-2,3-dione with benzene-1,2-diamine, benzene-1,3-diamine and benzene-1,4-diamine respectively. The reaction of Lo, Lm and Lp with Co(II) and Ni(II) halides gave the corresponding coordination complexes which were characterized by elemental analysis, molar conductance, infra-red, GC-MS and electronic spectral studies. Docking of the 1H-indole-2,3-diones toward the binding sites of penicillin binding protein and DNA gyrase showed they interacted favourably with the test antibacterial targets at deltaGs range of -2.51 to -5.48 kcal/mol. In accordance to literature report, coordination of cobalt and nickel to the ligands yielded metal complexes which exhibited improved interaction with the protein targets (at deltaGs range of -8.70 to -10.20 kcal/mol). In vitro antimicrobial studies against some microorganisms showed that some of the compounds were active against few Gram negative and Gram positive bacteria. The Lo, Lm and Lp had no activity against any of the test microorganisms but the Co(II) and Ni(II) complexes, showed antibacterial activity. The [Co(Lo)2] and [Ni(Lo)2] complexes generated the least antibacterial response. [Co(Lo)2] was ineffective against E. coli 6 and Staphylococcus sciuri subsp sciuri while Bacillus subtilis was resistant to [Ni(Lo)2] which moderately inhibited E. coli 14 (7 mm). Both compounds indicated zero activity against Pseudomonas aeruginosa. The complex that evoked the highest bactericidal activity were [CoLm]Cl2 and [NiLp]Cl2. The antibiogram activity of [CoLm]Cl2 was found between 20 and 30 mm with E. coli 6 displaying greater sensitivity (30 mm) and S. sciuri the least (20 mm). The activity of [NiLp]Cl2 complex indicate that the activity spectrum of the organisms occurred within 29 and 45 mm range; the least sensitive were E. coli 14 (29 mm) and B. subtilis (29 mm) while the most sensitive was S. sciuri subsp sciuri (45 mm). The two compounds were further studied for minimum inhibitory concentration (MIC) and their binding modes towards the studied protein targets were analyzed. Result indicate that the MIC of 1.25 ug/mL was determined for the complex ([NiLp]Cl2) against S. sciuri subsp sciuri (12 mm) while in case of [CoLm]Cl2, the MIC was 2.5 ug/mL (13 mm) against the same organism. The binding modes predicted for [CoLm]Cl2 and [NiLp]Cl2 identified essential residues necessary for interaction with the studied proteins and which could be targeted during structural/activity optimization.